Morbid obesity is an important public health problem, but the complex relationship between obesity and the skeleton is poorly understood. This proposal has been designed to examine the impact of obesity and obesity treatments on skeletal health, and to facilitate my long-term goal of becoming an independent clinical investigator. Recent epidemiologic data suggest that fracture rates in morbidly obese adults are higher than is commonly believed, and may equal or surpass rates in normal-weight adults at certain skeletal sites. Furthermore, Roux-en-Y gastric bypass surgery is becoming increasingly popular as a treatment for morbid obesity, but there is growing concern that the surgery results in accelerated bone loss and increased risk of fractures. Our knowledge in this field has been complicated by known limitations in dual-energy x-ray absorptiometry in obesity and during weight loss. This proposal seeks to provide a more complete and accurate evaluation of bone density, microarchitecture, and strength in both obesity and after gastric bypass surgery using advanced imaging techniques. A prospective, longitudinal cohort of morbidly obese adults will be studied before and for 2 years after gastric bypass surgery using quantitative computed tomography and high- resolution non-invasive imaging. Normal-weight and non-surgical obese controls will be recruited for cross-sectional and longitudinal comparisons. We will also examine the complex physiology connecting adipose tissue and the skeleton, and evaluate potential mechanisms of accelerated bone loss after gastric bypass. The career development plan consists of a five year mentored program that will incorporate didactic and research training and will be guided by well-established scientists who have been selected based upon their expertise in obesity and metabolic bone disease. In summary, the proposed research will test innovative hypotheses about the skeletal consequences of obesity and gastric bypass surgery, while providing a training platform and investigational niche for the candidate to establish independence as a clinical investigator. Characterization of obesity's effects on bone may yield insights on how to optimize skeletal health in obese patients, uncover ways to minimize fracture risk for patients undergoing gastric bypass surgery, and shed light on the complex interactions between adipose tissue and bone.
Severe obesity may be associated with defects in skeletal health, and weight-loss surgery may further lead to accelerated bone loss and increased risk of fractures. The proposed project will provide an in- depth analysis of the effects of obesity and weight-loss surgery on bone health. The knowledge gained from these studies will improve the clinical care of obese patients and those who are considering weight-loss surgery as well as shed light on the complex interplay between bone and adipose tissue.
|Lindeman, Katherine G; Greenblatt, Logan B; Rourke, Caroline et al. (2018) Longitudinal 5-Year Evaluation of Bone Density and Microarchitecture After Roux-en-Y Gastric Bypass Surgery. J Clin Endocrinol Metab 103:4104-4112|
|Yu, Elaine W; Lee, Moa P; Landon, Joan E et al. (2017) Fracture Risk After Bariatric Surgery: Roux-en-Y Gastric Bypass Versus Adjustable Gastric Banding. J Bone Miner Res 32:1229-1236|
|Yu, Elaine W; Greenblatt, Logan; Eajazi, Alireza et al. (2017) Marrow adipose tissue composition in adults with morbid obesity. Bone 97:38-42|
|Bredella, Miriam A; Greenblatt, Logan B; Eajazi, Alireza et al. (2017) Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density and marrow adipose tissue. Bone 95:85-90|
|Yu, Elaine W; Carmody, Jill S; Brooks, Daniel J et al. (2016) Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass. Bone 85:23-8|
|Yu, Elaine W; Wewalka, Marlene; Ding, Su-Ann et al. (2016) Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients With Type 2 Diabetes. J Clin Endocrinol Metab 101:714-22|
|Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L et al. (2016) Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women. J Clin Endocrinol Metab 101:3114-22|
|Yu, Elaine W; Bouxsein, Mary L; Putman, Melissa S et al. (2015) Two-year changes in bone density after Roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab 100:1452-9|
|Torriani, Martin; Oliveira, Adriana L; Azevedo, Debora C et al. (2015) Effects of Roux-en-Y gastric bypass surgery on visceral and subcutaneous fat density by computed tomography. Obes Surg 25:381-5|
|Yu, E W; Putman, M S; Derrico, N et al. (2015) Defects in cortical microarchitecture among African-American women with type 2 diabetes. Osteoporos Int 26:673-9|
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